The principal goal of this investigation is to determine the mechanisms of short-term and long-term control of the set of liver enzymes that catalyze the formation of long-chain fatty-acids. Although whole animal experiments are contemplated the principal experimental approach employs maintenance cultures of liver parenchymal cells (hepatocytes) that have been separated from whole liver by perfusion with collagenase. The response of these cells to added insulin and glucagon is evaluated in terms of the rate of incorporation of tritiated water (3H2O) or 14C-labelled acetate into fatty acids. Key lipogenic enzyme activity is also determined in the hepatocyte cytosol. Ultimately the rate of synthesis of these enzymes will be measured by pulse labelling with amino acids. Once the induction process is well characterized in cultured hepatocytes a delineation of preinduction events will be undertaken. These include: change in concentration and flux of key lipogenic precursors as a function of time following the insulin signal; change in concentration of the inactive (phosphorylated) and active (dephosphorylated) forms of pyruvate dehydrogenase, acetyl CoA carboxylase and the fatty acid synthetase complex as a function of preinduction time; and change in concentration of total and specific mRNA harvested from hepatocyte polysomes. Provided these studies show that hepatocytes cultured in vitro retain the principal features of events assosicated with the induction process in vivo an examination will be made of the pattern of phosphorylation of nonhistone proteins of liver nuclear chromatin.